In this study, we have investigated the anti-depressant effects of the fruit Areca catechu L. (ACL) and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress (CUMS).

CUMS was induced in rats to establish a depression animal model for 28 days. According to the baseline sucrose preference, the male rats were divided into 6 different groups. They were treated with paroxetine hydrochloride, ACL, and water once a day until the behavioral tests were performed. The levels of corticosterone (CORT), malondialdehyde (MDA), catalase (CAT), and total superoxide dismutase (T-SOD) in serum were detected using a commercial kit, and the concentrations of 5-hydroxytryptamine (5-HT) and dopamine (DA) monoamine neurotransmitters in the brain tissues were detected by liquid chromatography-tandem mass spectrometry. doublecortin (DCX) expression in the hippocampal dentate gyrus (DG) was determined by immunofluorescence, and the relative abundance of brain-derived neurotrophic factor (BDNF), TrkB, PI3K, p-AKT/AKT, PSD-95, and p-GSK-3β/GSK-3β of brain tissues were assayed by western blot.

ACL markedly increased sucrose preference, decreased the immobility time, and shortened the feeding latency of CUMS-induced rats. CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters (5-HT and DA) in the hippocampus and cortex of brain tissues and the levels of CORT, MDA, CAT, and T-SOD in serum, whereas ACL administration alleviated these considerable changes. ACL promoted DCX expression in DG and increased the protein levels of BDNF, TrkB, PI3K, p-AKT/AKT, PSD-95, and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.

Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic–pituitary–adrenal axis, stimulating hippocampal neurogenesis, and activating the BDNF signaling pathway.